Desialylated (i.e. neuraminidase-treated) lymphocytes (DL) induce significantly more cytotoxicity in isolated rabbit hepatocytes than do intact lymphocytes. This phenomenon can be selectively blocked by a desialylated glycoprotein and is attributed to the receptor for desialylated glycoproteins (hepatic binding protein, HBP) on the surface of hepatocytes interacting with its specific ligands on the surface of DL. Purified HBP increases the cytotoxicity of DL to target cells which do not bear HBP on their surface presumably by an analogous mechanism. Infused desialylated peripheral blood mononuclear cells (PBMC) and DL are selectively taken up by the liver in rabbits. The phenomenon is unaffected by depletion of complement but can be blocked by preincubation of desialylated PBMC with IgG-Fab fragments. These findings suggest that the selective hepatic uptake of desialylated PBMC or DL is not mediated by HBP. They are compatible with disialylated PBMC or DL becoming coated with naturally occurring antibodies in vivo with the result that subsequemnt recognition of cell bound antibody by Fc receptors on Kupffer cells mediates their selective hepatic uptake.